OBJECTIVES: Gelatinases (MMP2 and MMP9) are expressed in giant-cell arteritis (GCA) and are thought to play a role in vessel disruption. However, their activation status and enzymatic activity have not been evaluated. Our aim was to investigate the distribution and proteolytic activity of gelatinases in GCA lesions at different stages. METHODS: Expression of MMP2, MMP9, MMP2-activator MMP14 and their natural inhibitors TIMP1 and TIMP2 was determined by real-time PCR and immunohistochemistry in temporal artery sections from 46 patients and 12 controls. MMP activation status and enzymatic activity were assessed by gelatin and film in situ zymography. RESULTS: Vascular smooth muscle cells from normal specimens constitutively expressed pro-MMP2 and its inhibitor TIMP2 with no resulting proteolytic activity. In GCA MMP2, MMP9 and MMP14 were strongly expressed in their active form by infiltrating leucocytes. Inflamed arteries also expressed TIMP1 and TIMP2. However, the MMP9/TIMP1 and MMP2/TIMP2 ratios were higher in patients compared with controls, indicating an increased proteolytic balance in GCA which was confirmed by in situ zymography. Maximal gelatinase expression and activity occurred at the granulomatous areas surrounding the internal elastic lamina (IEL). Myointimal cells also expressed MMPs and exhibited proteolytic activity, suggesting a role for gelatinases in vascular remodelling and repair. CONCLUSIONS: GCA lesions show intense expression of gelatinases. Activators and inhibitors are regulated to yield enhanced gelatinase activation and proteolytic activity. Distribution of expression and proteolytic activity suggests that gelatinases have a major role not only in the progression of inflammatory infiltrates and vessel destruction but also in vessel repair.
OBJECTIVES: Gelatinases (MMP2 and MMP9) are expressed in giant-cell arteritis (GCA) and are thought to play a role in vessel disruption. However, their activation status and enzymatic activity have not been evaluated. Our aim was to investigate the distribution and proteolytic activity of gelatinases in GCA lesions at different stages. METHODS: Expression of MMP2, MMP9, MMP2-activator MMP14 and their natural inhibitors TIMP1 and TIMP2 was determined by real-time PCR and immunohistochemistry in temporal artery sections from 46 patients and 12 controls. MMP activation status and enzymatic activity were assessed by gelatin and film in situ zymography. RESULTS: Vascular smooth muscle cells from normal specimens constitutively expressed pro-MMP2 and its inhibitor TIMP2 with no resulting proteolytic activity. In GCA MMP2, MMP9 and MMP14 were strongly expressed in their active form by infiltrating leucocytes. Inflamed arteries also expressed TIMP1 and TIMP2. However, the MMP9/TIMP1 and MMP2/TIMP2 ratios were higher in patients compared with controls, indicating an increased proteolytic balance in GCA which was confirmed by in situ zymography. Maximal gelatinase expression and activity occurred at the granulomatous areas surrounding the internal elastic lamina (IEL). Myointimal cells also expressed MMPs and exhibited proteolytic activity, suggesting a role for gelatinases in vascular remodelling and repair. CONCLUSIONS: GCA lesions show intense expression of gelatinases. Activators and inhibitors are regulated to yield enhanced gelatinase activation and proteolytic activity. Distribution of expression and proteolytic activity suggests that gelatinases have a major role not only in the progression of inflammatory infiltrates and vessel destruction but also in vessel repair.
Authors: Satyajit K Karnik; Benjamin S Brooke; Antonio Bayes-Genis; Lise Sorensen; Joshua D Wythe; Robert S Schwartz; Mark T Keating; Dean Y Li Journal: Development Date: 2003-01 Impact factor: 6.868
Authors: Jennifer Dien; Hesham M Amin; Neil Chiu; Winson Wong; Christine Frantz; Brian Chiu; John R Mackey; Raymond Lai Journal: Am J Pathol Date: 2006-08 Impact factor: 4.307
Authors: M C Cid; M Cebrián; C Font; B Coll-Vinent; J Hernández-Rodríguez; J Esparza; A Urbano-Márquez; J M Grau Journal: Arthritis Rheum Date: 2000-01
Authors: José Hernández-Rodríguez; Marta Segarra; Carme Vilardell; Montse Sánchez; Ana García-Martínez; María-José Esteban; Josep M Grau; Alvaro Urbano-Márquez; Dolors Colomer; Hynda K Kleinman; Maria C Cid Journal: Circulation Date: 2003-05-12 Impact factor: 29.690
Authors: Maria C Cid; José Hernández-Rodríguez; María-José Esteban; Mireia Cebrián; Yong Song Gho; Carme Font; Alvaro Urbano-Márquez; Josep M Grau; Hynda K Kleinman Journal: Circulation Date: 2002-09-24 Impact factor: 29.690
Authors: Alicia Rodríguez-Pla; Francisco Martínez-Murillo; Peter J Savino; Ralph C Eagle; Philip Seo; Mark J Soloski Journal: Rheumatology (Oxford) Date: 2009-09-06 Impact factor: 7.580
Authors: Alicia Rodriguez-Pla; Roscoe L Warner; David Cuthbertson; Simon Carette; Nader A Khalidi; Curry L Koening; Carol A Langford; Carol A McAlear; Larry W Moreland; Christian Pagnoux; Philip Seo; Ulrich Specks; Antoine G Sreih; Steven R Ytterberg; Kent J Johnson; Peter A Merkel; Paul A Monach Journal: J Rheumatol Date: 2019-09-01 Impact factor: 4.666
Authors: Christian Dejaco; Elisabeth Brouwer; Justin C Mason; Frank Buttgereit; Eric L Matteson; Bhaskar Dasgupta Journal: Nat Rev Rheumatol Date: 2017-09-14 Impact factor: 20.543
Authors: Dan Pugh; Maira Karabayas; Neil Basu; Maria C Cid; Ruchika Goel; Carl S Goodyear; Peter C Grayson; Stephen P McAdoo; Justin C Mason; Catherine Owen; Cornelia M Weyand; Taryn Youngstein; Neeraj Dhaun Journal: Nat Rev Dis Primers Date: 2022-01-06 Impact factor: 65.038
Authors: Sudha Visvanathan; Mahboob U Rahman; Gary S Hoffman; Stephen Xu; Ana García-Martínez; Marta Segarra; Ester Lozano; Georgina Espígol-Frigolé; José Hernández-Rodríguez; Maria C Cid Journal: Rheumatology (Oxford) Date: 2011-08-25 Impact factor: 7.580
Authors: Sergio Prieto-González; Ana García-Martínez; Itziar Tavera-Bahillo; José Hernández-Rodríguez; José Gutiérrez-Chacoff; Marco A Alba; Giuseppe Murgia; Georgina Espígol-Frigolé; Marcelo Sánchez; Pedro Arguis; Maria C Cid Journal: Medicine (Baltimore) Date: 2015-02 Impact factor: 1.889